(1) Field of the Invention
This invention relates to a method for separating glycine and L-serine from a solution containing both of them. More particularly, it relates to a method for isolating and recovering the L-serine formed by a fermentation or enzymic conversion process using glycine as the raw material.
L-serine is a compound useful as a constituent of solutions for use in infusion, as a raw material of the preparation of drugs, and as an intermediate for the synthesis of amino acids such as tryptophan and the like.
(2) Description of the Prior Art
A large number of processes for the preparation of L-serine by using glycine as the raw material are known. They include, for example, enzymic conversion processes such as a process for preparing L-serine from glycine and formalin in the presence of tetrahydrofolic acid as a coenzyme by using a microorganism capable of producing L-serine hydroxymethyltransferase (E.C. 2.1.2.1) (Japanese patent Laid-Open No. 81691/'78) and a process for the preparation of L-serine by bringing glycine into contact with a microorganism capable of converting glycine to L-serine and then recovering the L-serine so formed (Japanese patent Laid-Open No. 130490/'78); processes for the preparation of L-serine by growing a microorganism in a glycine-containing medium so as to accumulate L-serine in the medium (Japanese patent Laid-Open Nos. 31995/'83, 88798/'81, 37169/'80, 29906/80, 26875/'80 and 72893/'78); and the like.
However, such processes for the preparation of L-serine by using glycine as the raw material involve difficulty in separating the L-serine formed as a reaction product from the glycine remaining in the reaction solution.
For example, where glycine is converted to L-serine by means of an enzyme such as L-serine hydroxymethyltransferase or the like, this conversion is based on an equilibrium reaction in which the degree of conversion of glycine to L-serine is always not greater than 75% and usually not greater than 50%. Accordingly, the resulting reaction solution always contains both glycine and L-serine, which are very difficult to separate.
Since the solubility of glycine in water (22% at 20.degree. C. in the neutral pH range) is very close to that of L-serine (18%), it is very difficult to separate only one of them from the reaction solution by utilizing the difference in solubility between them.
For that reason, the aforementioned Japanese patent Laid-Open No. 31995/'83 discloses a method for the isolation of L-serine by utilizing the difference in solubility in the m-xylene-4-sulfonic acid salts of glycine and L-serine. However, this method requires troublesome operations and fails to give a satisfactorily high yield, so that it cannot be regarded as practicable for industrial purposes.
On the other hand, a number of conventional methods for the separation of amino acids by using a strongly acidic ion exchange resin are known as described, for example, in Japanese patent Laid-Open No. 72893/'78. In the present case, however, the isoelectric point of glycine (5.97) is very close to that of L-serine (5.68). Thus, it is difficult to separate them and recover glycine by an ordinary adsorption and elution procedure based on the exchange of ions. According to the invention of the aforementioned Japanese patent, a method for the separation of glycine and L-serine has been proposed in which, on the basis of the fact that their isoelectric points change differently with the pH of the solution, they are separated by repeating their adsorption to and elution from a strongly acidic ion exchange resin while gradually varying the pH of the solution by means of a buffer such as citric acid or the like. However, this method fails to separate them satisfactorily and, moreover, requires troublesome operations. Accordingly, this method cannot be considered to be an industrially practicable one.
Thus, it has been impossible to separate glycine and L-serine efficiently, even when a strongly acidic ion exchange resin is used. For this reason, even if glycine used as the raw material can be converted to L-serine at a considerable degree of conversion, the L-serine cannot be isolated and recovered in a satisfactorily high yield. Moreover, it is unavoidable to waste an appreciable portion of the expensive glycine used as the raw material. These disadvantages eventually raise the overall product cost of L-serine.